The object of this research is to elucidate the mechanisms by which steroid hormones produce their physiological effects. The primary long- term goal is the description of the entire sequence of molecular and metabolic events between hormone interactions with the cells and the emergence of changes at the cellular level. The principal focus of the proposed research will be to unravel the intermediate steps in the overall sequence of events involved in glucocorticoid action in rat thymus cells. The approach planned is the identification, in the context of the relevance to the generation of the late catabolic effects, the physiologically significant initial hormone- induced metabolic alterations, and to establish the nature of the metabolic interrelationships between these early and late hormone actions. Specifically, continuing studies will investigate the relationship between early cortisol action on glucose metabolism and the later actions on macromolecular metabolism with reference to a working hypothesis that hormone effects on the latter are the result of an inhibition of carbohydrate-supported ATP generation for biosynthetic reactions. Studies are also proposed whose aim is establishing the role of the immediate stimulatory effects of glucocorticoids on RNA and protein synthesis in the sequence of events between hormone binding and the initial action on glucose metabolism.